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Title: Prostaglandin E2/EP1 signaling pathway enhances intercellular adhesion molecule 1 (ICAM-1) expression and cell motility in oral cancer cells. Author: Yang SF, Chen MK, Hsieh YS, Chung TT, Hsieh YH, Lin CW, Su JL, Tsai MH, Tang CH. Journal: J Biol Chem; 2010 Sep 24; 285(39):29808-16. PubMed ID: 20647315. Abstract: Oral squamous cell carcinoma has a striking tendency to migrate and metastasize. Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin (PG) synthase, has been implicated in tumor metastasis. However, the effects of COX-2 on human oral cancer cells are largely unknown. We found that overexpression of COX-2 or exogenous PGE(2) increased migration and intercellular adhesion molecule 1 (ICAM)-1 expression in human oral cancer cells. Using pharmacological inhibitors, activators, and genetic inhibition of EP receptors, we discovered that the EP1 receptor, but not other PGE receptors, is involved in PGE(2)-mediated cell migration and ICAM-1 expression. PGE(2)-mediated migration and ICAM-1 up-regulation were attenuated by inhibitors of protein kinase C (PKC)δ, and c-Src. Activation of the PKCδ, c-Src, and AP-1 signaling pathway occurred after PGE(2) treatment. PGE(2)-induced expression of ICAM-1 and migration activity were inhibited by a specific inhibitor, siRNA, and mutants of PKCδ, c-Src, and AP-1. In addition, migration-prone sublines demonstrated that cells with increased migration ability had higher expression of COX-2 and ICAM-1. Taken together, these results indicate that the PGE(2) and EP1 interaction enhanced migration of oral cancer cells through an increase in ICAM-1 production.[Abstract] [Full Text] [Related] [New Search]